1. Field of the Invention
This invention relates to novel naphthoquinone compositions and the pharmaceutical use of the naphthoquinones in treating psoriasis in a mammal.
2. Prior Art
Psoriasis is a skin disease characterized in part by excessive proliferation of cells of the epidermis which remain strongly adherent and build up into a scaly plaque typical of the disease. Currently available therapies, which are not curative, depend on the control of epidermal cell proliferation through the use of hormonal agents, such as corticosteroids, or through the use of compounds related to cancer chemotherapy such as hydroxyurea, methotrexate, and the nitrogen mustards.
While the above agents are effective to a certain extent, they cause numerous severe undesirable side effects both locally and systemically.
Certain naphthoquinones which are chemically related to the compound of this invention are known. For example, the compound 6-bromo-2,3-dihydroxy-1,4naphthoquinone has been reported by Weygand, German Pat. No. 859,008. While this compound is recognized as a valuable intermediate for the preparation of dyestuffs, no useful biological activity has been ascribed to it. Specifically, any suggestion that this compound might have anti-psoriatic activity has not been advanced.
Related naphthoquinones having antifungal and antibacterial activity can be found in U.S. Pat. No. 3,914,264 and West German Offenlegungschrift Nos. 2,135,712, 2,456,655 and 2,520,739. However, none of these disclosures have recognized the use of these or related naphthoquinone compositions as anti-psoriatic agents.
It is also suggested that certain related compounds have antimalarial activitu, e.g. 6-chloro-2-hydroxy-1,4-naphthoquinone, 7-chloro-2-hydroxy-1,4-naphthoquinone and 6-chloro-1,2,4-triacetoxynaphthoquinone. See L. F. Fieser and R. H. Brown, J. Am. Chem. Soc. 71, 3615-3617 (1949).
It has now been discovered that the 2,3-diesters of 6-substituted-2,3-dihydroxy-1,4-naphthoquinone are effective in preventing epidermal cell proliferation when topically applied to a mammal. More specifically, it is effective as an anti-psoriatic agent in humans.
In its broadest aspect, the present invention is a pharmaceutical composition comprising at least one pharmaceutically acceptable excipient and a 2,3-diester of a 6-substituted-2,3-dihydroxy-1,4-naphthoquinone represented by Formula (I), below, ##STR1## wherein R is hydrogen, halo, cyano, C.sub. 1 to C.sub. 18 linear or branched alkoxy and R.sup.1 is an alkyl of 1-5 carbon atoms. Preferably R is halo (particularly chloro) and R.sup.1 is alkyl of 1 or 2 carbon atoms.
Another aspect of this invention is a method for preventing epidermal cell proliferation in a mammal which comprises topically administering a composition of the invention to a mammal in need of such treatment.